Neurocritical Care Update: From Monitoring to Management

Dr Neeraj Manikath , claude.ai

Abstract

Neurocritical care has evolved dramatically over the past decade, transitioning from crude clinical assessments to sophisticated multimodal monitoring systems, and from blanket treatment protocols to precision medicine approaches. This review synthesizes contemporary evidence in three critical domains: multimodal neuromonitoring in traumatic brain injury (TBI), the evolving landscape of targeted temperature management (TTM), and novel therapeutic paradigms in refractory status epilepticus (RSE). We highlight actionable clinical pearls derived from recent trials and emerging technologies that are reshaping bedside decision-making for critically ill neurological patients.

Introduction

The neurocritical care unit (NCCU) represents the intersection of neurology, neurosurgery, and critical care medicine—a specialty that demands both technological sophistication and clinical acumen. With over 69 million people worldwide suffering traumatic brain injuries annually, approximately 50,000 cases of status epilepticus in the United States alone, and cardiac arrest affecting 350,000 Americans each year, the stakes in neurocritical care have never been higher[1,2]. This review focuses on three transformative areas where recent evidence is changing practice: multimodal monitoring in TBI, temperature management strategies, and the management of refractory status epilepticus.

Multimodal Monitoring in Traumatic Brain Injury: Making Sense of the Data

The Evolution Beyond ICP

For decades, intracranial pressure (ICP) monitoring served as the cornerstone of TBI management. However, the BEST:TRIP trial demonstrated that ICP monitoring alone, without integration of other physiological parameters, may not improve outcomes in resource-limited settings[3]. This paradox—that monitoring ICP doesn't necessarily improve outcomes—forced a paradigm shift toward multimodal monitoring that captures the complexity of secondary brain injury.

The Monitoring Arsenal

Intracranial Pressure and Cerebral Perfusion Pressure ICP monitoring remains foundational, but contemporary practice emphasizes maintaining individualized CPP targets (typically 60-70 mmHg) rather than universal thresholds[4]. The concept of "optimal CPP" (CPPopt)—derived from continuous pressure reactivity monitoring—allows patient-specific targets based on cerebrovascular autoregulation status.

Brain Tissue Oxygenation (PbtO₂) Brain tissue oxygen monitoring has emerged as a powerful adjunct. The BOOST-II trial and subsequent meta-analyses suggest that PbtO₂-guided therapy (maintaining values >20 mmHg) may reduce mortality and improve functional outcomes[5]. Pearl: PbtO₂ monitoring is particularly valuable in scenarios where CPP appears adequate but regional hypoxia persists—the "talking and dying" phenomenon of traumatic contusions.

Cerebral Microdialysis Microdialysis catheters measure cerebral metabolic markers including lactate, pyruvate, glucose, and glycerol in the extracellular fluid. A lactate/pyruvate ratio >40 indicates mitochondrial dysfunction and predicts poor outcomes[6]. Oyster: While microdialysis provides unparalleled metabolic insight, its focal nature means catheter placement is critical—ideally in perilesional "at-risk" tissue rather than frank necrosis or normal brain.

Continuous EEG and Spreading Depolarizations Continuous EEG (cEEG) identifies non-convulsive seizures in approximately 20% of comatose TBI patients[7]. Emerging technology can detect cortical spreading depolarizations (CSDs)—waves of neuronal depolarization associated with metabolic crisis and expansion of contusions. Hack: In centers without CSD monitoring, recognizing clustered spreading depression-like patterns on cEEG may prompt intensified metabolic support.

Integrating the Data: From Numbers to Decisions

The challenge isn't acquiring data—it's interpretation. Modern approaches use multimodality informatics to identify physiological crises:

The PRx (Pressure Reactivity Index): Correlates slow waves of ICP with MAP to assess cerebrovascular autoregulation. A PRx >0.3 indicates impaired autoregulation and predicts poor outcomes[8].
Integrated Monitoring Algorithms: Commercial platforms now integrate ICP, CPP, PbtO₂, and temperature into single displays with automated crisis detection.
The "Physiological Storm" Concept: Simultaneous derangements in multiple parameters (elevated ICP + low PbtO₂ + mitochondrial dysfunction on microdialysis + impaired autoregulation) demand aggressive, multimodal intervention.

Clinical Pearl for Practice: Establish institutional protocols that define specific interventions for different monitoring patterns:

Isolated ICP elevation → Optimize head position, sedation, osmotherapy
ICP + low PbtO₂ → Augment CPP, consider increased FiO₂, evaluate for ischemia
Normal ICP + low PbtO₂ → Investigate regional perfusion (CT perfusion/angiography)
Metabolic crisis on microdialysis → Aggressive glucose management, consider metabolic support

The Pragmatic Approach: Not all centers can implement full multimodal monitoring. Prioritize based on TBI severity: ICP alone for moderate TBI, add PbtO₂ for severe TBI with contusions or diffuse injury, and reserve microdialysis for refractory cases or research protocols.

Targeted Temperature Management: New Evidence, New Protocols

The Fall and Rise of Therapeutic Hypothermia

The history of temperature management in neurocritical care resembles a pendulum. Initial enthusiasm for deep hypothermia (32-34°C) following the landmark 2002 trials in post-cardiac arrest care gave way to disappointment when the TTM trial (2013) showed no benefit of 33°C versus 36°C[9]. The subsequent TTM2 trial (2021) further challenged dogma by demonstrating non-superiority of 33°C versus normothermia with fever prevention in out-of-hospital cardiac arrest[10].

Current Evidence-Based Recommendations

Post-Cardiac Arrest Care The 2021 AHA/ILCOR guidelines now recommend preventing fever (maintaining <37.5°C) rather than mandating specific hypothermia targets[11]. This represents a shift from aggressive cooling to meticulous temperature control. Pearl: The critical element isn't achieving 33°C—it's avoiding hyperthermia, particularly in the first 72 hours when fever is independently associated with poor neurological outcomes.

Traumatic Brain Injury Early enthusiasm for hypothermia in TBI was tempered by the Eurotherm3235 trial, which was stopped early due to worse outcomes in the hypothermia arm[12]. The culprit? Achieving hypothermia often required increased ICP (by lowering CPP), creating secondary injury. Oyster: Prophylactic hypothermia in TBI is not recommended, but targeted cooling for refractory intracranial hypertension remains a salvage option when other measures fail.

Acute Ischemic Stroke The EuroHYP-1 trial showed no benefit of 34-35°C hypothermia in acute ischemic stroke[13]. However, fever prevention remains standard care in stroke units.

The New Frontier: Precision Temperature Management

Individualized Temperature Targets Emerging evidence suggests temperature sensitivity varies by injury mechanism and patient factors. Consider:

Shivering threshold determination: Use surface cooling technologies (Arctic Sun, CureWrap) that minimize shivering burden
Inflammatory phenotyping: Patients with high inflammatory markers (elevated IL-6, CRP) may benefit more from aggressive temperature control
Genetic variants: Polymorphisms in genes like CACNA1A may predict temperature sensitivity, though this remains investigational

Duration and Rewarming The "rewarming injury" phenomenon is increasingly recognized. Rapid rewarming (>0.5°C/hour) can trigger rebound intracranial hypertension, hyperkalemia, and hemodynamic instability[14]. Hack: Program cooling devices for controlled rewarming at 0.2-0.3°C per hour, with continuous ICP monitoring during rewarming in TBI patients.

Practical Protocol for Temperature Management

Tier 1: Universal Fever Prevention

Maintain core temperature <37.5°C
Acetaminophen 1g q6h (standard unless contraindicated)
Surface cooling devices for temperature >38°C
Investigate and treat infection sources aggressively

Tier 2: Targeted Cooling (Select Cases)

Target 35-36°C for refractory ICP elevation after TBI
Consider 36°C for selected post-cardiac arrest patients with extensive comorbidities
Implement full cooling protocol: sedation, neuromuscular blockade if shivering refractory to buspirone/meperidine, electrolyte monitoring

Tier 3: Advanced Temperature Modulation

Endovascular cooling for precise temperature control
Extended temperature management (>48 hours) in selected cases
Continuous multimodal monitoring during cooling and rewarming phases

Clinical Pearl: The most underappreciated aspect of temperature management is electrolyte disturbances. During cooling, anticipate hypomagnesemia, hypophosphatemia, and hypokalemia; during rewarming, expect rebound hyperkalemia and hypoglycemia.

Managing Refractory Status Epilepticus: From Anesthesia to Immunotherapy

Defining the Problem

Status epilepticus (SE) becomes refractory (RSE) when seizures persist despite two appropriate antiseizure medications, occurring in approximately 30-40% of SE cases[15]. Super-refractory status epilepticus (SRSE) denotes SE lasting >24 hours despite anesthesia—a catastrophic condition with mortality approaching 30-50%[16].

The Anesthetic Approach: Evolution Beyond Burst Suppression

First-Line Anesthetics: What Changed? Traditional teaching mandated targeting burst suppression on EEG. However, the 2023 ESETT trial challenged this dogma by showing similar efficacy between levetiracetam, fosphenytoin, and valproate for established SE[17]. For RSE, current evidence suggests:

Midazolam vs. Propofol vs. Pentobarbital

Midazolam: Easier titration, less hypotension, but breakthrough seizures more common
Propofol: Intermediate efficacy, propofol infusion syndrome risk limits duration
Pentobarbital: Most effective seizure suppression but highest hemodynamic complications

Pearl: A 2019 meta-analysis found no mortality difference between agents, suggesting choice should be guided by comorbidities: midazolam for hemodynamic instability, propofol for short-term control, pentobarbital for refractory cases[18].

The EEG Target Debate Burst suppression (BS) has been the traditional goal, but seizure cessation may be adequate. A 2020 study suggested that titrating to seizure freedom rather than BS reduced anesthetic duration without worsening outcomes[19]. Hack: Use quantitative EEG metrics—aim for suppression ratio 50-80% if targeting BS, but accept lower ratios if seizures terminate and don't recur.

Beyond Anesthesia: The Emerging Role of Immunotherapy

The recognition that immune mechanisms drive many SRSE cases has revolutionized management. Consider antibody-mediated encephalitis in:

Young patients without prior epilepsy
Prominent psychiatric features or movement disorders
MRI showing mesial temporal or cortical inflammation
CSF lymphocytic pleocytosis

The Immunotherapy Arsenal

First-Line Immunotherapy (initiate within 7 days if immune etiology suspected):

Methylprednisolone: 1g IV daily × 5 days
IVIG: 2g/kg divided over 2-5 days
Plasma exchange: Consider if IVIG/steroids ineffective after 5-7 days

Second-Line Immunotherapy (SRSE persisting >14 days):

Rituximab: 375 mg/m² weekly × 4 doses (targets B-cells, particularly effective in NMDA-receptor encephalitis)
Cyclophosphamide: 750-1000 mg/m² monthly (reserve for severe, refractory cases)
Tocilizumab: IL-6 receptor antagonist, emerging evidence in refractory autoimmune encephalitis[20]

Clinical Pearl: Don't wait for antibody results to initiate immunotherapy—send comprehensive panels (NMDA-R, LGI1, CASPR2, GAD65, AMPA-R, GABA-B-R) but start empiric immunotherapy if clinical suspicion is high. Antibody tests can take weeks, and delayed treatment worsens outcomes.

Novel and Emerging Therapies

Ketogenic Diet The ketogenic diet (4:1 ratio) can be initiated via nasogastric tube in SRSE patients. Meta-analyses suggest seizure cessation in 50-60% of SRSE cases, typically within 2-10 days[21]. Hack: Use ketogenic formulations (KetoCal) rather than attempting to formulate diet in the ICU—consistency is critical.

Allopregnanolone (Brexanolone) This GABA-A receptor modulator, FDA-approved for postpartum depression, has shown promise in case series of SRSE, particularly in GABAA-receptor antibody encephalitis[22].

Cannabidiol While evidence is limited to case reports, high-dose CBD (up to 25-50 mg/kg/day) has terminated SRSE in select cases, particularly febrile infection-related epilepsy syndrome (FIRES)[23].

Electroconvulsive Therapy (ECT) ECT has demonstrated efficacy in treatment-refractory SRSE, hypothesized to work via seizure-induced neuroplasticity and anti-inflammatory effects. Consider in cases failing pharmacological and immunological interventions[24].

A Practical Algorithm for RSE/SRSE Management

Phase 1 (0-24 hours): Standard RSE Protocol

Continuous anesthetic (midazolam/propofol/pentobarbital)
Load additional ASMs (lacosamide, levetiracetam, valproate)
Aggressive etiology workup (MRI, LP, metabolic panel, toxicology, autoimmune panel)

Phase 2 (24-72 hours): Early Immunotherapy Consideration

If clinical features suggest autoimmune etiology → start IVIG/methylprednisolone
Initiate ketogenic diet
Consider perampanel (AMPA antagonist) as adjunct ASM

Phase 3 (>72 hours): SRSE Protocol

Rituximab if autoimmune features persist
Consider novel agents (allopregnanolone, CBD, magnesium sulfate)
Multidisciplinary discussion regarding ECT
Plan for anesthetic wean trial (slow taper over 24-48 hours while monitoring cEEG)

Oyster: Many SRSE patients have cryptogenic etiology despite exhaustive workup. These patients may have neuronal surface antibody-negative autoimmune encephalitis or genetic epilepsies that present de novo. Empiric immunotherapy is still reasonable if other features are suggestive.

Conclusion: Toward Personalized Neurocritical Care

The common thread uniting these three domains—TBI monitoring, temperature management, and status epilepticus—is the shift from protocol-driven care to individualized, physiology-based medicine. Rather than universal ICP targets, we pursue optimal autoregulation ranges. Instead of blanket hypothermia, we provide precision temperature control tailored to injury mechanism. Rather than anesthetizing all RSE identically, we phenotype patients and select immunotherapy, dietary interventions, or novel agents accordingly.

The neurocritical care unit of 2025 increasingly resembles a physiology laboratory where continuous data streams inform dynamic interventions. Success requires not just technological capability but clinical wisdom—knowing when aggressive monitoring and intervention improve outcomes versus when they simply complicate dying.

Final Pearl for Practice: In neurocritical care, the most important monitor isn't the ICP transducer, the EEG machine, or the cooling device—it's the experienced clinician at the bedside synthesizing multimodal data into coherent clinical action. Technology augments, but never replaces, clinical judgment.

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Conflict of Interest: None declared.

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Thursday, November 6, 2025